The renin-angiotensin system is involved in the homeostatic function to control systemic blood pressure, the volume of body fluid, balance among the electrolytes, etc., associated with the aldosterone system. Development of angiotensinII converting enzyme inhibitors (ACE inhibitor: this converting enzyme produces angiotensinII which possesses a strong vasoconstrictive action) has clarified the relation between the renin-angiotensin system and hypertension. Since angiotensinII constricts blood vessels to elevate blood pressure via the angiotensinII receptors on the cellular membranes, angiotensinII antagonists, like the ACE inhibitor, would be useful in treating hypertension caused by angiotensinII.
It has been reported that various angiotensinII analogues such as saralasin, [Sar.sup.1,Ile.sup.8 ]AII, and the like, possess potent angiotensinII antagonist activity.
It has, however, been reported that, when peptide antagonists are administered parenterally, their actions are not prolonged and, when administered orally, they are ineffective (M. A. Ondetti and D. W. Cushman, Annual Reports in Medicinal Chemistry, 13, 82-91 (1978)).
It would be highly desirable to develop a non-peptide angiotensinII antagonist which overcomes these drawbacks. In the earliest studies in this field, imidazole derivatives having angiotensinII antagonist activity have been disclosed in Japanese Patent Laid Open No. 71073/1981; No. 71074/1981; No. 98270/1982; and No. 157768/1983; U.S. Pat. Nos. 4,355,040; and 4,340,598, etc. Later, improved imidazole derivatives were disclosed in European Patent Laid Open No. 0253310; No. 0291969; No. 0324377; and No. 403158, WO No. 9100277, and Japanese Patent Laid Open No. 23868/1988; and No. 117876/1989. Further, pyrrole, pyrazole, and triazole derivatives are disclosed as angiotensinII antagonists in European Patent Laid Open No. 0323841; and No. 0409332, and Japanese Patent Laid Open No. 287071/1989. Benzimidazole derivatives are disclosed as angiotensinII antagonists in U.S. Pat. No. 4,880,804, European Patent Laid Open No. 0392317, No. 0399732, and No. 0400835, and Japanese Patent Laid Open No. 63264/1991. Azaindene derivatives are disclosed as angiotensinII antagonists in European Patent Laid Open No. 0399731. Pyrimidone derivatives are disclosed as angiotensinII antagonists in European Patent Laid Open No. 0407342. Quinazoline derivatives are disclosed as angiotensinII antagonists in European Patent Laid Open No. 0411766.
It is considered that clinically useful angiotensinII antagonistic compounds for practical use are required to have a prolonged potent angiotensinII antagonistic by oral administration and the activity of even the above disclosed prior art compounds is insufficient for clinical uses.